CXA4_HUMAN
ID CXA4_HUMAN Reviewed; 333 AA.
AC P35212; A8K698; D3DPR4; Q9P106; Q9UBL1; Q9UNA9; Q9UNB0; Q9UNB1; Q9Y5N7;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 183.
DE RecName: Full=Gap junction alpha-4 protein;
DE AltName: Full=Connexin-37;
DE Short=Cx37;
GN Name=GJA4;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=7680674; DOI=10.1172/jci116321;
RA Reed K.E., Westphale E.M., Larson D.M., Wang H.-Z., Veenstra R.D.,
RA Beyer E.C.;
RT "Molecular cloning and functional expression of human connexin37, an
RT endothelial cell gap junction protein.";
RL J. Clin. Invest. 91:997-1004(1993).
RN [2]
RP SEQUENCE REVISION.
RA Beyer E.C.;
RL Submitted (OCT-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS SER-71; VAL-128; ILE-130
RP AND SER-319.
RA van Zeijl L., Cotgreave I.A.;
RT "A connexin 37 genotypic variant in atherosclerosis.";
RL Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS ILE-130 AND SER-319.
RA Kumari S., Varadaraj K., Valiunas V., Ramanan S.V., Beyer E.C., Brink P.R.;
RT "Functional expression and biophysical properties of two polymorphic forms
RT of human connexin37.";
RL Submitted (AUG-1999) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Lench N.J., Williams G., Williams E., Gharani N., Franks S.;
RT "Connexin 37 mutation screening in anovulatory polycystic ovary syndrome.";
RL Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Ovary, Pancreas, and Spleen;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP VARIANT ILE-130.
RX PubMed=8761439; DOI=10.1093/carcin/17.8.1761;
RA Krutovskikh V., Mironov N., Yamasaki H.;
RT "Human connexin 37 is polymorphic but not mutated in tumours.";
RL Carcinogenesis 17:1761-1763(1996).
RN [11]
RP VARIANT SER-319.
RX PubMed=10447790; DOI=10.1046/j.1365-2796.1999.00564.x;
RA Boerma M., Forsberg L., Van Zeijl L., Morgenstern R., De Faire U.,
RA Lemne C., Erlinge D., Thulin T., Hong Y., Cotgreave I.A.;
RT "A genetic polymorphism in connexin 37 as a prognostic marker for
RT atherosclerotic plaque development.";
RL J. Intern. Med. 246:211-218(1999).
RN [12]
RP VARIANT SER-319.
RX PubMed=10728596;
RX DOI=10.1002/(sici)1097-0215(20000401)86:1<67::aid-ijc10>3.0.co;2-1;
RA Saito T., Krutovskikh V., Marion M.J., Ishak K.G., Bennett W.P.,
RA Yamasaki H.;
RT "Human hemangiosarcomas have a common polymorphism but no mutations in the
RT connexin37 gene.";
RL Int. J. Cancer 86:67-70(2000).
CC -!- FUNCTION: One gap junction consists of a cluster of closely packed
CC pairs of transmembrane channels, the connexons, through which materials
CC of low MW diffuse from one cell to a neighboring cell.
CC -!- SUBUNIT: A connexon is composed of a hexamer of connexins.
CC -!- INTERACTION:
CC P35212; P60033: CD81; NbExp=3; IntAct=EBI-6918707, EBI-712921;
CC P35212; Q5J8X5: MS4A13; NbExp=3; IntAct=EBI-6918707, EBI-12070086;
CC P35212; P35372: OPRM1; NbExp=3; IntAct=EBI-6918707, EBI-2624570;
CC P35212; Q8N661: TMEM86B; NbExp=3; IntAct=EBI-6918707, EBI-2548832;
CC P35212; Q96FB2; NbExp=3; IntAct=EBI-6918707, EBI-2857623;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. Cell
CC junction, gap junction.
CC -!- TISSUE SPECIFICITY: Expressed in multiple organs and tissues, including
CC heart, uterus, ovary, and blood vessel endothelium.
CC -!- SIMILARITY: Belongs to the connexin family. Alpha-type (group II)
CC subfamily. {ECO:0000305}.
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DR EMBL; M96789; AAA52558.2; -; mRNA.
DR EMBL; AF139100; AAD31869.1; -; Genomic_DNA.
DR EMBL; AF139101; AAD31870.1; -; Genomic_DNA.
DR EMBL; AF139102; AAD31871.1; -; Genomic_DNA.
DR EMBL; AF139103; AAD31872.1; -; Genomic_DNA.
DR EMBL; AF139104; AAD31873.1; -; Genomic_DNA.
DR EMBL; AF139105; AAD31874.1; -; Genomic_DNA.
DR EMBL; AF181620; AAD56940.1; -; mRNA.
DR EMBL; AF132674; AAF62342.1; -; Genomic_DNA.
DR EMBL; AK291563; BAF84252.1; -; mRNA.
DR EMBL; AL121988; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471059; EAX07440.1; -; Genomic_DNA.
DR EMBL; CH471059; EAX07441.1; -; Genomic_DNA.
DR EMBL; BC027889; AAH27889.1; -; mRNA.
DR EMBL; BC072389; AAH72389.1; -; mRNA.
DR CCDS; CCDS30669.1; -.
DR PIR; I55593; I55593.
DR RefSeq; NP_002051.2; NM_002060.2.
DR RefSeq; XP_005270807.1; XM_005270750.2.
DR RefSeq; XP_016856532.1; XM_017001043.1.
DR AlphaFoldDB; P35212; -.
DR SMR; P35212; -.
DR BioGRID; 108968; 8.
DR IntAct; P35212; 7.
DR MINT; P35212; -.
DR STRING; 9606.ENSP00000343676; -.
DR TCDB; 1.A.24.1.6; the gap junction-forming connexin (connexin) family.
DR iPTMnet; P35212; -.
DR PhosphoSitePlus; P35212; -.
DR BioMuta; GJA4; -.
DR DMDM; 8928555; -.
DR MassIVE; P35212; -.
DR PaxDb; P35212; -.
DR PeptideAtlas; P35212; -.
DR PRIDE; P35212; -.
DR Antibodypedia; 4590; 309 antibodies from 31 providers.
DR DNASU; 2701; -.
DR Ensembl; ENST00000342280.5; ENSP00000343676.4; ENSG00000187513.9.
DR GeneID; 2701; -.
DR KEGG; hsa:2701; -.
DR MANE-Select; ENST00000342280.5; ENSP00000343676.4; NM_002060.3; NP_002051.2.
DR UCSC; uc001bya.3; human.
DR CTD; 2701; -.
DR DisGeNET; 2701; -.
DR GeneCards; GJA4; -.
DR HGNC; HGNC:4278; GJA4.
DR HPA; ENSG00000187513; Low tissue specificity.
DR MIM; 121012; gene.
DR neXtProt; NX_P35212; -.
DR OpenTargets; ENSG00000187513; -.
DR PharmGKB; PA28689; -.
DR VEuPathDB; HostDB:ENSG00000187513; -.
DR eggNOG; ENOG502QU20; Eukaryota.
DR GeneTree; ENSGT01050000244914; -.
DR InParanoid; P35212; -.
DR OMA; KDPHVER; -.
DR OrthoDB; 903777at2759; -.
DR PhylomeDB; P35212; -.
DR TreeFam; TF329606; -.
DR PathwayCommons; P35212; -.
DR Reactome; R-HSA-190861; Gap junction assembly.
DR SignaLink; P35212; -.
DR BioGRID-ORCS; 2701; 9 hits in 1066 CRISPR screens.
DR GeneWiki; GJA4; -.
DR GenomeRNAi; 2701; -.
DR Pharos; P35212; Tbio.
DR PRO; PR:P35212; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P35212; protein.
DR Bgee; ENSG00000187513; Expressed in tibial artery and 142 other tissues.
DR ExpressionAtlas; P35212; baseline and differential.
DR Genevisible; P35212; HS.
DR GO; GO:0005922; C:connexin complex; IEA:Ensembl.
DR GO; GO:0005921; C:gap junction; TAS:ProtInc.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0005243; F:gap junction channel activity; IBA:GO_Central.
DR GO; GO:0001568; P:blood vessel development; IEA:Ensembl.
DR GO; GO:0006816; P:calcium ion transport; IEA:Ensembl.
DR GO; GO:0007043; P:cell-cell junction assembly; TAS:ProtInc.
DR GO; GO:0007267; P:cell-cell signaling; IBA:GO_Central.
DR GO; GO:0003158; P:endothelium development; IEA:Ensembl.
DR GO; GO:0048265; P:response to pain; IEA:Ensembl.
DR Gene3D; 1.20.1440.80; -; 1.
DR InterPro; IPR000500; Connexin.
DR InterPro; IPR002263; Connexin37.
DR InterPro; IPR019570; Connexin_CCC.
DR InterPro; IPR017990; Connexin_CS.
DR InterPro; IPR013092; Connexin_N.
DR InterPro; IPR038359; Connexin_N_sf.
DR PANTHER; PTHR11984; PTHR11984; 1.
DR Pfam; PF00029; Connexin; 1.
DR PRINTS; PR00206; CONNEXIN.
DR PRINTS; PR01134; CONNEXINA4.
DR SMART; SM00037; CNX; 1.
DR SMART; SM01089; Connexin_CCC; 1.
DR PROSITE; PS00407; CONNEXINS_1; 1.
DR PROSITE; PS00408; CONNEXINS_2; 1.
PE 1: Evidence at protein level;
KW Cell junction; Cell membrane; Gap junction; Membrane; Reference proteome;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..333
FT /note="Gap junction alpha-4 protein"
FT /id="PRO_0000057814"
FT TOPO_DOM 1..20
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 21..40
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 41..76
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 77..99
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 100..148
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 149..165
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 166..207
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 208..230
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 231..333
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 292..333
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VARIANT 71
FT /note="P -> S"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_009159"
FT VARIANT 128
FT /note="A -> V (in dbSNP:rs147128480)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_009160"
FT VARIANT 130
FT /note="V -> I (in dbSNP:rs41266431)"
FT /evidence="ECO:0000269|PubMed:8761439, ECO:0000269|Ref.3,
FT ECO:0000269|Ref.4"
FT /id="VAR_009161"
FT VARIANT 319
FT /note="P -> S (in allele CX37*2; dbSNP:rs1764391)"
FT /evidence="ECO:0000269|PubMed:10447790,
FT ECO:0000269|PubMed:10728596, ECO:0000269|Ref.3,
FT ECO:0000269|Ref.4"
FT /id="VAR_009162"
SQ SEQUENCE 333 AA; 37414 MW; 93AD224531E5EAD2 CRC64;
MGDWGFLEKL LDQVQEHSTV VGKIWLTVLF IFRILILGLA GESVWGDEQS DFECNTAQPG
CTNVCYDQAF PISHIRYWVL QFLFVSTPTL VYLGHVIYLS RREERLRQKE GELRALPAKD
PQVERALAAV ERQMAKISVA EDGRLRIRGA LMGTYVASVL CKSVLEAGFL YGQWRLYGWT
MEPVFVCQRA PCPYLVDCFV SRPTEKTIFI IFMLVVGLIS LVLNLLELVH LLCRCLSRGM
RARQGQDAPP TQGTSSDPYT DQVFFYLPVG QGPSSPPCPT YNGLSSSEQN WANLTTEERL
ASSRPPLFLD PPPQNGQKPP SRPSSSASKK QYV
